Microbial Product Cocktails for Personalized Cancer Immunotherapy

Yue Yan, Sijia Yang, Kathleen E. Mach, Guoli Chen, David J. DeGraff, Joseph C. Liao () and Pak Kin Wong ()
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Yue Yan: The Pennsylvania State University, Department of Biomedical Engineering
Sijia Yang: The Pennsylvania State University, Department of Biomedical Engineering
Kathleen E. Mach: Stanford University School of Medicine, Department of Urology
Guoli Chen: Hershey Medical Center, Department of Pathology and Laboratory Medicine, Penn State Health Milton S.
David J. DeGraff: Hershey Medical Center, Department of Pathology and Laboratory Medicine, Penn State Health Milton S.
Joseph C. Liao: Stanford University School of Medicine, Department of Urology
Pak Kin Wong: The Pennsylvania State University, Department of Biomedical Engineering

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract The human immune system has evolved to interact with various commensal and pathogenic bacteria in intricate and nuanced ways. While the diversity of bacteria presents fundamental challenges in understanding immune-microbe interactions, it also offers ample opportunities for developing effective immunomodulatory therapies. Here we show microbial product cocktails as an alternative class of immunotherapy for cancer. Using freshly resected tumors from bladder cancer patients, an immuno-comparative analysis of recruitment and enhancement assay, and an artificial intelligence-guided optimization workflow, we establish a personalized platform for identifying potent microbial product cocktails that promote recruitment, infiltration, and activation of immune cells for cancer treatment. In an orthotopic mouse bladder cancer model, microbial product cocktails demonstrate immunoenhancement and improve survival rates compared with standard bacillus Calmette–Guérin immunotherapy.

Date: 2025
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DOI: 10.1038/s41467-025-66238-1

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